Tiotropium bromide is an anticholinergic with specificity for muscarinic receptors. It therefore provides therapeutic benefit in the treatment of asthma or chronic obstructive pulmonary disease (“COPD”).
The chemical name of Tiotropium bromide is (1α, 2β, 4β, 5α, 7β)-7-[(hydroxydi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.0]nonane bromide or 6β, 7β-epoxy-3β-hydroxy-8-methyl-1αH, 5αH-tropanium bromide, di-2-thienylglycolate, and it has the following structure:

Tiotropium bromide is available commercially as SPIRIVA® HandiHaler®, available from Boehringer Ingelheim, in which it is present as the monohydrate form.
The preparation and crystallization of Tiotropium bromide from acetone and methanol is disclosed in U.S. Pat. No. 5,610,163, providing a product having a melting point of 217-218° C.
Crystalline forms of Tiotropium bromide have also been reported in various publications, such as U.S. Pat. No. 6,777,423, which describes a crystalline-Tiotropium bromide monohydrate, U.S. Pat. No. 6,608,055, which describes a crystalline form of Tiotropium bromide anhydrate, WO 2005/042527 which describes another crystalline form of anhydrous Tiotropium bromide, and Publication No. IPCOM000143595D which describes a crystalline dichloromethane solvate of Tiotropium bromide.
The occurrence of different crystal forms (polymorphism) is a property of some molecules and molecular complexes. A single molecule, like the Tiotropium bromide in the above formula, may give rise to a variety of solids having distinct physical properties like melting point, X-ray diffraction pattern, infrared absorption fingerprint and NMR spectrum. The differences in the physical properties of polymorphs result from the orientation and intermolecular interactions of adjacent molecules (complexes) in the bulk solid. Accordingly, polymorphs are distinct solids sharing the same molecular formula, yet the polymorphs have distinct advantageous and/or disadvantageous physical properties compared to other forms in the polymorph family. One of the most important physical properties of pharmaceutical polymorphs is their solubility in aqueous solution.
The discovery of new crystalline polymorphic forms of a drug enlarges the repertoire of materials that a formulation scientist has available with which to design a pharmaceutical dosage form of a drug with a targeted release profile and/or other desired characteristics. Therefore, there is a need to find additional crystalline forms of Tiotropium bromide.
Similar advantages can come from new solvates which may lead to other polymorphs, may provide a better way to produce still other forms or solvates, or may provide processing advantages.